Cancers and malignant tumors are characterized by continuous cell proliferation and cell death and are related causally to both genetics and the environment. In developed countries, colorectal cancer is the second most commonly diagnosed cancer, and 95% of the cancers are adenocarcinomas. These cancers are slow growing, and a long interval may elapse before symptoms emerge. Early detection of colorectal cancer significantly impacts survival. A fact of note is that colon cancer is more common in women, and rectal cancer is more common in men. Colorectal cancers spread by direct extension through the bowel wall and metastasis.
Although genetic predisposition is low, colon cancer families include familial adenomatous polyposis, caused by inherited mutations in the APC gene, and hereditary nonpolyposis colorectal cancer, caused by mutations in DNA mismatch repair genes leading to increased replication errors in microsatellites. These syndromes are known to occur across several generations and usually present before age 40. Unknown genetic susceptibility factors are thought to occur in “sporadic” colon cancers, because risk increases with persons having first-degree relatives that develop colon cancer before the age of 60 (Cohen et al. In: DeVita (2001) Cancer: Principles and Practice of Oncology. Lippincott Williams & Wilkins, Philadelphia Pa., pp. 1148–1149.
Cancer markers are of importance in determining familial predisposition to cancers. For example, even though elevated serum carcinoembryonic antigen (CEA) is not specifically associated with colorectal cancer, its levels are high in 70% of patients. If CEA is high preoperatively and low after removal of a colon tumor, monitoring CEA may help to detect recurrence. In addition, key genes in several molecular pathways may be activated, or genes suppressing cell proliferation may be lost by mutation or by hypermethylation (Wafik et al. (1991) Proc Natl Acad Sci 88:3470–3474; Issa et al. (1994) Nature Genet 7:536–540). Among these are well known tumor suppressors, APC and p53, transmembrane receptors such as the EGF receptor and the guanlylyl cyclase C receptor (Bradley et al. (1986) Arch Surg 121:1242–7), G-protein activators such as Ras, and markers associated with CpG islands (Jass et al. (2000) Histopathology 37:295–301). Tumor markers more specifically associated with particular colorectal cancers would be of even greater diagnostic and prognostic utility.
Array technologies and quantitative PCR provide the means to explore the expression profiles of a large number of related or unrelated genes. When an expression profile is examined, arrays provide a platform for examining which genes are tissue-specific, carrying out housekeeping functions, parts of a signaling cascade, or specifically related to a particular genetic predisposition, condition, disease, or disorder. The application of expression profiling is particularly relevant to improving diagnosis, prognosis, and treatment of the disease. For example, both the sequences and the amount of expression can be compared between tissues from subjects with different types of colon cancer and cytologically normal colon tissue.
The discovery of a transmembrane protein, its encoding cDNA, and the making of an antibody that specifically binds the protein satisfies a need in the art by providing compositions which are useful to diagnose, to stage, to treat, or to monitor the progression or treatment of neoplastic disorders and in particular colon and lung cancers.